This application to participate in the CCTRN proposes clinical research skills development program and phase l/ll randomized clinical trial evaluating the safety and efficacy of novel cell-based therapeutic strategy for idiopathic dilated cardiomyopathy (IDCM), a leading cause of heart failure (HF), death and disability. This trial will have major impact in the field of cell-baed therapy for IDCM as new approach to produce durable and sustainable improvements in heart function and to cause reverse remodeling. This trial is built on solid foundation of extensive preclinical and clinical work demonstrating that: 1) intramyocardial cell delivery can be safely and effectively performed using catheter based system in HF patients, and 2) bone marrow-derived mesenchymal stem cells (MSCs) are well tolerated, engraft in injured tissues, and stimulate endogenous cardiac stem cell (CSC) proliferation and differentiation. Accordingly, the hypothesis to be tested is that combining CSCs and MSCs will enhance the therapeutic efficacy relative to use of MSCs alone. The mechanism of action at phenotypic level will be assessed using cardiac MRI to measure regional and global LV function, tissue fibrosis, and tissue perfusion. Post-hoc analysis will be performed to test the hypothesis that in vitro assessments of cell morphology, cell surface markers, and cell colony growth potential may predict ability of individual patient's cells to improve cardiac measures. Cellular mechanisms of action of MSC therapy will be assessed by measuring capacity for endogenous CSC proliferation and differentiation. Endomyocardial biopsies will be obtained and tested for their capacity to yield endogenous CSCs. Our group has extensive experience with catheter delivery of MSCs in patients with ischemic and non-ischemic HF. Accordingly, this study is timely, warranted, and may have major health impact by addressing unmet need in IDCM patients. This program will break new ground in field by testing novel therapeutic approach, combining two cell types that together have synergistic properties demonstrated biologically. Together, these aims will advance our understanding of cell-based therapy for IDCM, with specific emphasis placed upon parameters of patient selection, cell delivery strategies, and the impact of novel cell formulations.